Epoxide hydrolases are cellular enzymes that catalyze the conversion of epoxides to dihydrodiols. Because epoxides are highly reactive electrophiles, they are common ultimate toxins, mutagens, and carcinogens. The capability of epoxide hydrolases to convert these reactive intermediates to less reactive products places them among the most important endogenous means of protection against chemical toxins and carcinogens. The purpose of these studies is to examine several epoxide hydrolases, to compare and contrast their structural and catalytic properties, and to investigate their participation in the metabolism of toxic compounds. Understanding the nature of these multiple epoxide hydrolases and their participation in the deactivation of epoxide intermediates is essential to our ultimate understanding of mechanisms of chemical toxicity and carcinogenesis. The emphasis of these studies is on the examination of different epoxide hydrolases derived from different organs, species, and individuals. Of specific interest is the possible polymorphism of epoxide hydrolases in man. The existence of multiple enzyme forms in man may represent a significant genetically regulated determinant of different individual responses to chemical toxins and carcinogens.